Abstract

Background: Monitoring the host immune response to tumors in the cancer microenvironment helps predict treatment response and outcome. Tumor-infiltrating lymphocytes (TILs), which are indicators for monitoring an immune response, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focus on TILs that exist within the FF and we have performed pathological evaluations. Among patients undergoing neoadjuvant chemotherapy (NAC) for breast cancer, we evaluated the prediction of treatment effects using FF-TILs. Methods: Of the 320 patients were treated with NAC, 239 subjects who were able to evaluate FF-TILs were targeted. The FF is a converged focus of the tissue component of the stroma of a tumor, and it is surrounded by infiltrating tumor cells. Lymphocytes that infiltrate the FF are FF-TILs. Results: The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p < 0.001, log-rank) and for all subtypes of triple-negative breast cancer (TNBC) (p = 0.001, log-rank), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p = 0.010, log-rank), and hormone receptor-positive breast cancer (HRBC) (p = 0.003, log-rank). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases (p < 0.001, hazard ratio (HR) = 0.198) and all subtypes of TNBC (p = 0.006, HR = 0.172), HER2BC (p = 0.025, HR = 0.135), and HRBC (p = 0.007, HR = 0.228). Conclusions: It is suggested that FF-TILs are a useful factor for predicting recurrence of breast cancer after NAC. Legal entity responsible for the study: Shinichiro Kashiwagi Funding: None Disclosure: All authors have declared no conflicts of interest.

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